Study of AMG 330 in Combination With Pembrolizumab in Adult With Relapsed or Refractory Acute Myeloid Leukemia

Relapsed or Refractory Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase 1b Study Assessing Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 330 cIV in Combination With Pembrolizumab in Adult Subjects With Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04478695
• Other study ID #: 20170646
• Secondary ID: KEYNOTE-613
• Status: Terminated
• Phase: Phase 1
• Start date: September 29, 2020
• Est. completion date: October 23, 2020

Study information

• Verified date: June 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the safety and tolerability of AMG 330, administered in combination with pembrolizumab, in participants with relapsed or refractory acute myeloid leukemia (R/R AML).

Description:

This study will assess the safety and tolerability of AMG 330 in combination with pembrolizumab and whether pembrolizumab will enhance the anti-AML activity of AMG 330. Both cohort 1 and 2 will include AMG 330 and pembrolizumab with the difference being the initiation date for pembrolizumab treatment.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: October 23, 2020
• Est. primary completion date: October 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

Key Inclusion criteria

• AML as defined by the WHO Classification persisting or recurring following one or more treatment courses. Except APL

• Eastern Cooperative Oncology Group (ECOG) =1

Key Exclusion criteria

• Active extramedullary AML in the central nervous system.

• Known hypersensitivity to immunoglobulins.

• Non-manageable graft versus host disease.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Relapsed or Refractory Acute Myeloid Leukemia

Intervention

Drug:
• AMG 330
Continuous intravenous (IV) infusion.
• Pembrolizumab
Intravenous (IV) infusion.

Locations

Country	Name	City	State
United States	City of Hope National Medical Center	Duarte	California
United States	University of Texas MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Amgen	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)	A DLT was defined as any of the events described below occurring in a participant during the DLT window, unless clearly attributable to causes other than investigational product: Any treatment-related death, Grade 4 neutropenia, Grade 3-4 non hematologic toxicity not clearly resulting from the underlying leukemia, with some exceptions, cytokine release syndrome, and any Grade 5 toxicity.	28 days
Primary	Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	A TEAE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment that occurred after first dose. Any clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests that occurred after first dose were recorded as TEAEs.	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.
Primary	Number of Participants Who Experienced Treatment-related Adverse Events (TRAEs)	A TRAE was defined as any untoward medical occurrence in a clinical study participant considered to have a possible causal relationship with the study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests that were considered to have a possible causal relationship with the study treatment were recorded as TRAEs.	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.
Secondary	Complete Remission Without Minimal Residual Disease (CRMRD-)	CRMRD- was measured according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017). CRMRD- was defined as complete remission (CR) with negativity for a genetic marker by quantitative reverse transcription polymerase chain reaction (RT-qPCR), or CR with negativity by multiparametric flow cytometry (MFC). CR was defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) = 1.0 x 109/L (1000/µL); platelet count = 100 x 109/L (100 000/µL).	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.
Secondary	Complete Remission (CR)	CR was measured according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017). CR was defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) = 1.0 x 109/L (1000/µL); platelet count = 100 x 109/L (100 000/µL).	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.
Secondary	CR With Incomplete Recovery (CRi)	CRi was measured according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017). CRi was defined as all CR criteria (bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) = 1.0 x 109/L (1000/µL); platelet count = 100 x 109/L [100 000/µL]), except for residual neutropenia (< 1.0 x 109/L [1000/µL]) or thrombocytopenia (< 100 x 109/L [100 000/µL]).	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.
Secondary	Morphological Leukemia-free State (MLFS)	MLFS was measured according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017). MLFS was defined as bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required.	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.
Secondary	Partial Remission (PR)	PR was measured according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017). PR was defined as all hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25%; and decrease of pre-treatment bone marrow blast percentage by at least 50%.	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.
Secondary	Duration of Response (DoR)	DoR was calculated for participants who achieved overall response (CRMRD-, CR, CRi, PR or MLFS). DoR was defined as time from the first observation indicating an objective response to the subsequent date of disease progression or death, whichever is earlier.	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.
Secondary	Plasma Concentration of AMG 330		Pre-dose, 6hrs post-dose Day 1 to 71 of Cycle 1 (Cycle 1=77 days), pre-dose, 6hrs post-dose Day 1 to 50 of Cycles 2+ (Cycle 2+=57 days); end of infusion,0.5,2,4 and 8hrs post-infusion on Days 78 and 57 of Cycle 1 and 2 infusion-free periods respectively
Secondary	Half-life of AMG 330		Pre-dose, 6hrs post-dose Day 1 to 71 of Cycle 1 (Cycle 1=77 days), pre-dose, 6hrs post-dose Day 1 to 50 of Cycles 2+ (Cycle 2+=57 days); end of infusion,0.5,2,4 and 8hrs post-infusion on Days 78 and 57 of Cycle 1 and 2 infusion-free periods respectively
Secondary	Steady State Concentration of AMG 330		Pre-dose, 6hrs post-dose Day 1 to 71 of Cycle 1 (Cycle 1=77 days), pre-dose, 6hrs post-dose Day 1 to 50 of Cycles 2+ (Cycle 2+=57 days); end of infusion,0.5,2,4 and 8hrs post-infusion on Days 78 and 57 of Cycle 1 and 2 infusion-free periods respectively
Secondary	Volume of Distribution of AMG 330		Pre-dose, 6hrs post-dose Day 1 to 71 of Cycle 1 (Cycle 1=77 days), pre-dose, 6hrs post-dose Day 1 to 50 of Cycles 2+ (Cycle 2+=57 days); end of infusion,0.5,2,4 and 8hrs post-infusion on Days 78 and 57 of Cycle 1 and 2 infusion-free periods respectively
Secondary	Clearance of AMG 330		Pre-dose, 6hrs post-dose Day 1 to 71 of Cycle 1 (Cycle 1=77 days), pre-dose, 6hrs post-dose Day 1 to 50 of Cycles 2+ (Cycle 2+=57 days); end of infusion,0.5,2,4 and 8hrs post-infusion on Days 78 and 57 of Cycle 1 and 2 infusion-free periods respectively
Secondary	Number of Participants With Anti-AMG 330 Antibody Formation		From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.

External Links

•   AmgenTrials clinical trials website